Wittig-Homer-Emmons reaction

The formation of flve-membered cyclic imines through a Staudinger/intramolecular aza-Wittig reaction can also be performed by solid-phase synthesis and has been applied for the first synthesis of lanopylin Bi (108). The total synthesis, which takes only four steps, starts with a phase-transfer alkylation of diethyl 2-oxopropylphosphonate 105 with a 2-iodoethyl azide, affording the azido phosphonate 106, which undergoes a phase-transfer Homer-Emmons Wittig reaction with heptadecanal to provide the azido enone 107. An intramolecular aza-Wittig reaction of the enone 107 with polymer-supported triphenylphosphine in toluene completed the first total synthesis of lanopylin Bi (108) in 76% yield (Scheme 15.22). 

Many solid-phase syntheses that involve the extension of ir-conjugated systems are known in the literature. Heck, Stille, Suzuki, Homer-Emmons, Wittig, and other metal-induced coupling reactions were all demonstrated to work on solid supports, some at relatively high yields [154—156]. Table 7.2 summarizes some of these reactions with respect to conditions and yields many other examples may be found in the literature. 

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

An important modification to the Wittig reaction is the use of stabilized phosphonate carbanions in olefin synthesis. This reaction, originally discovered by Homer but developed by Wadsworth and Emmons, is used extensively for transformation of a carbonyl... 

The (Homer-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a,/l-unsaturated esters, a,/l-unsaturated ketones and other conjugated systems. Yields are often better then with the original Wittig procedure. However the Wadsworth-Emmons method is not suitable for the preparation of alkenes with simple, non-stabilizing alkyl substituents. 

Several variants of the Wittig olefination reaction have been adapted to solid phase (Fig. 8). Williard et al. [43] prepared a series of stilbenes using the Homer-Emmons reaction on resin-bound aldehydes. A route to either substituted or unsubstituted unsatu-... 

Pauson-Khand cycloaddition Pictet-Spengler reaction Ugi four-component condensation Wittig reaction (and Homer-Emmons condensation)... 

The Homer-Wadsworth-Emmons reaction represents a methodologically more important and more commonly used supplement to the Wittig reaction (cf. Section 11.1.3) than the Wittig-Homer reaction (Section 11.2). 

Alternatives to the standard Wittig reaction have been developed, including the Homer-Wadsworth-Emmons (HWE) reaction which involves the reaction of a phosphonate stabilized carbanion with a carbonyl compound (Scheme 2). These carbanions are generally more reactive than the traditional phosphoranes and they will often react with ketones that are unreactive to stabilized phosphoranes.2 3,8... 

SCHEME 6.68 The Homer-Emmons modification of the Wittig reaction is a generally useful alternative to the standard Wittig reaction. 

---